1. Field of the Invention
Valproate (sodium di-n-propylacetate) is recognized as an important antiepileptic drug. Its use as an anticonvulsant is beneficial due to its low toxicity. A minimum level of 50 .mu.g/ml in serum is required for therapeutic efficacy; however, this level is often difficult to maintain due to individual differences in serum absorption and metabolism. It is therefore essential to monitor the serum levels regularly in order to insure that a minimum therapeutic level of valproate is being maintained.
Of the current assay procedures for valproate, vapor phase chromatography analysis is the most widely used. Known techniques have various inadequacies in being uneconomical, slow and/or requiring trained clinicians to perform the assay properly. It is therefore desirable to provide a simple and rapid procedure for determining valproate levels in serum or other physiological fluids, which provides reproducible values and is specific for valproate.
The simple structure of vaproic acid--a saturated branched aliphatic acid--makes it one of the smallest and simplest drugs to be considered as a hapten-protein antigen for production of antibodies. As such, in the design of any hapten derivatives of valproic acid, to be used in the conjugation to proteins for the preparation of antigenic conjugates, there is little guidance as to the effect of structural modification on the specificity of antibodies.
2. Description of the Prior Art
Matsumoto et al., "Mass Spectrometry in Drug Metabolism" by Frigero and Ghesalberli, Plenum Publishing Corp., New York, N.Y. (1977) and Kuhara & Matsumoto, Biomedical Mass Spectrometry, 1, 291 (1974) teach that valproic acid is metabolized in humans via oxidation predominantly at the positions .beta. and .omega. to the carboxylic acid, and is eventually excreted in urine as the free acids or via glucuronide formation. U.S. Pat. No. 3,817,837 describes a homogeneous enzyme immunoassay technique for the determination of a wide variety of drugs.